Experiencing chronic stress day after day can produce
wear and tear on the body physically and mentally,
and can have a detrimental effect on learning and
emotion. However, acute stress -- a short stressful
incident -- may enhance learning and memory.

Researchers at the University at Buffalo have shown,
in trials using rodents as an animal model, that acute
stress can produce a beneficial effect on learning
and memory, through the effect of the stress hormone
corticosterone (cortisol in humans) on the brain's
prefrontal cortex, a key region that controls learning
and emotion.

Specifically, they demonstrated that acute stress
increases transmission of the neurotransmitter glutamate
and improves working memory.

"Stress hormones have both protective and damaging
effects on the body," said Zhen Yan, professor
of physiology and biophysics at UB and senior author
on the study. "This paper and others we have
in the pipeline explain why we need stress to perform
better, but don't want to be stressed out."

The study appeared July 20 in the online edition
of Proceedings of the National Academy of Sciences
and will be published in an upcoming print version
of the journal. Eunice Y. Yuen, Ph.D., UB research
assistant professor of physiology and biophysics,
is the first author on the study.

To test the effect of acute stress on working memory,
Yan, Yuen and colleagues trained rats in a maze until
they could complete it correctly 60-70 percent of
the time. When the rodents reached this level of accuracy
for two consecutive days, half were put through a
20-minute forced swim, which served as acute stress,
and then were put through the maze again.

Results showed that the stressed rats made significantly
fewer mistakes as they went through the maze both
four hours after the stressful experience and one
day post-stress, compared to the non-stressed rats.

To determine if the corticosterone neuropathway was
responsible for the improved memory, as they proposed,
researchers injected one group of rats before the
stressful forced-swim with a medicinal compound that
blocks the pathway, and injected another group with
saline. Results showed that the saline group, in which
the corticosterone neuropathway was not blocked, performed
better in the maze than the blocked group.

The researchers also determined that the stressful
experience did not increase depression or anxiety-related
behavior in the animals.

"It is known that stress has both positive and
negative actions in the brain, but the underlying
mechanism is elusive," said Yan. "Several
key brain regions involved in cognition and emotions,
including the prefrontal cortex, have been identified
as the primary target of corticosteroid, the major
stress hormone.

"Our current study identifies a novel mechanism
that underlies the impact of acute stress on working
memory, a cognitive process depending on glutamate
receptor-mediated excitatory signals in prefrontal
cortex circuits."

The investigators have expanded this research in
several directions. In a paper currently under review,
they have identified the key signaling molecules that
link acute stress to the enhancement of glutamate
receptors and working memory.

"In addition," noted Yan, "we have
discovered that chronic stress suppresses the transmission
of glutamate in the prefrontal cortex of male rodents,
which is opposite to the facilitating effect of acute
stress, and that estrogen receptors in female rodents
make them more resilient to chronic stress than male
rats.

"All these studies should bring new insights
into the complex actions of stress in different circumstances
that may be applicable to humans in the future,"
she said.

Wenhua Liu, Ph.D., postdoctoral associate, and Jain
Feng, Ph.D., associate professor, both in the UB Department
of Physiology and Biophysics, are co-authors on the
study, along with Ilia N. Karatsoreos, Ph.D., and
Bruce S. McEwen, Ph.D., from The Rockefeller University.